Peroxidases represent a group of hemoproteins that are ubiquitous in both the plant and animal kingdoms. They reduce H202 and other organic peroxides, while oxidizing a great variety of chemicals. During this reaction, free radicals are produced, which can bind irreversibly to DNA. In certain tissues which are low in the level of xenobiotic-biotransforming cytochrome P-450s, it could be possible that peroxidases provide alternate pathways for xenobiotic metabolism. Furthermore, the reaction of cytochrome P-450s with substrates is composed of a series of steps, one of which is similar to the peroxidative reaction. This also suggests the evolutionary relationship between cytochrome P-450s and peroxidases. Therefore, the studies on the peroxidases in terms of the regulation of their expression and the structure- function relationships will help in the understanding of those of the cytochrome P-450s. Although peroxidases exist throughout the human body, the levels and the types of peroxidases in different tissues are not clear. The thyroid gland is one of the tissues whose peroxidase has been intensely studied. This peroxidase is involved in thyroid hormone synthesis and recently has been indicated to be one of the major antigens of the thyroid autoimmune diseases such as Graves' disease and Hashimoto's thyroiditis. The level of the peroxidase is high in patients with the former disease and low in patients having the latter disease and also thyroid cancer. We have started characterization of the thyroid peroxidase by means of molecular biology. Two cDNA clones for human thyroid peroxidase were isolated and sequenced. Both cDNAs are identical except that the 171-nucleotide sequence is deleted in one of the clones, without any reading frame shift. Two mRNAs are expressed in all thyroid tissues examined, suggesting that the alternative splicing of the same gene generated two thyroid peroxidases.